What is Nutrigenomics?

Nutrigenomics researchers are trying to uncover interactions between diet and gene expression.

Photo: Courtesy Alltech Staff

The future of feeding horses is here: Learn how diet can impact your horse right down to his genetic core.

The field of equine nutrition has become quite sophisticated since the age when most horses roamed grasslands, wild, grazing day in and day out. In the years following their widespread domestication, most horses were allotted only a small area of land to graze and their diets were supplemented with grains and other concentrates. Now, some horses hardly graze at all and instead receive a complete balanced ration twice or thrice daily.

One look at the hundreds of feed and supplement options available shows us we’re not in our parents’ feed store, either. Yet even with all of the advancements, we are on the cusp of a new era: the nutrigenomics generation.

“Researchers are studying how nutrients, forms of nutrients, and nutritional strategies can influence an animal’s genome,” explains Kristen Brennan, PhD, project leader for equine nutrition and animal nutrigenomics at international animal health company Alltech Inc. “Our team measures what genes are turned on or off in response to feeding of nutrients, which allows them to better understand the science behind the idea that ‘you are what you eat.’”

She says equine microarrays—tools researchers use to assess the turning on and off of genes mentioned above—have become available only recently, and they might help her and other nutrition and/or genomics researchers better understand how a horse’s diet can influence his overall health.

In this article we will describe the growing field of nutrigenomics and its potential to benefit horses and maximize their good health.

What is Nutrigenomics?

More specifically, “the term ‘nutrigenomics’ is used to describe how nutrients interact, directly or indirectly, with an animal or individual’s genome to influence how genes are expressed and how those nutrients can impact health, disease, and even enhance performance,” says Brennan.

Let’s first briefly review genetics: DNA is the “core” of each and every one of our cells. The genes, subunits of this DNA, serve as a blueprint for mRNA, which translates into proteins. These proteins are long chains of amino acids that are the body’s “workhorses.” They serve both structural (i.e., forming tendons, ligaments, muscles) and functional roles (e.g., producing enzymes that can digest nutrients and playing a role in metabolizing nutrients to generate energy).

The term “gene expression” refers to how the genes produce proteins. Genes can undergo upregulation to produce more of a specific mRNA or downregulation to produce less of a specific mRNA. Scientists have long known that specific nutrients can interact with genomic traits to impact a horse’s health. Examples of this include the equine genetic diseases hyperkalemic periodic paralysis (HYPP) and polysaccharide storage myopathy (PSSM).

“In the case of HYPP, it is well-known that dietary management can decrease both the severity and frequency of HYPP attacks,” says Samantha Brooks, PhD, assistant professor of equine genetics and principal investigator in Cornell University’s Brooks Equine Genetics Laboratory, in Ithaca, N.Y. “Specifically, horses with HYPP should not be fed high-potassium feeds such as alfalfa and molasses, should be fed several small meals throughout the day, and need to be maintained with good, consistent hydration.”

In a nutshell, a gene chip is a small plate of glass encased in plastic that looks something like a computer microchip and is the size of a postage stamp. On the surface are thousands of short DNA sequences that make up specific genes. A researcher obtains a DNA sample from the patient, chops it into smaller pieces, dyes it, and applies it to the chip. He or she can then scan the chip to measure the amount of dyed DNA that binds to it.

Photo: Courtesy Affymetrix Inc.

Similarly, scientists know a predominantly grain diet can impact PSSM, and they encourage owners of affected horses to feed a low-carbohydrate, high-fat diet. Manufacturers have taken note, developing several feeds directed specifically toward these horses. So, owners have managed both HYPP and PSSM for years by altering the nutrients in their horse’s diet. The study of nutrigenomics, however, extends beyond simply altering feed to help horses with genetic diseases.

“We can make progress on these conditions by feeding individual horses exactly what they need based on how their body functions as determined by their DNA,” Brooks explains. “In the future, we can use their genetic makeup to predict where they might get into trouble and try to avoid issues altogether.”

Prior to the availability of the equine gene chip, which DNA microarray manufacturer Affymetrix released commercially last year, molecular analysis in horses was limited to custom arrays that measure expression of about 2,000 to 3,000 genes (compared to 50,000 with the commercial chip). But researchers at Alltech and at other institutions and companies can now get a picture of what is going on inside a horse’s cells in response to a product as a whole or a specific nutrient, both in healthy and disordered horses.

Brennan describes one recent study an Alltech research team conducted in which they examined how one of their products influenced metabolic markers in healthy horses and in horses with reduced insulin sensitivity. While the team took general health measurements, such as blood glucose and insulin, they also looked at how genes responded to the product. Researchers are in the process of analyzing this data, hoping to extract information that will help them determine what is happening inside the horse.

“Ultimately, this type of research will help us understand how we can precisely feed animals based on their genetic makeup,” explains Brennan. “Nutrigenomics provides a novel and more sophisticated means of measuring the impact of a nutrient on an animal. It gives us an idea of what is going on inside the animals’ cells to elicit a physiological response.”

How Nutrigenomics is Possible

In 2007 the equine genome was made public. In concert with that microscopic miracle came many other mini-miracles. One is a DNA “chip” (also called an SNP or single nucleotide polymorphism chip) that measures small changes in an animal’s genetic code. The second is the DNA microarray, or the gene chip described, which measures how genes turn on and off.

“DNA chips can be used for mapping, to discover genes linked to osteochondritis dissecans, for example, whereas gene chips and arrays, used for experiments like the one Brennan describes, are used to watch the genes, see which ones change in response to a change in diet, and learn a little more about the biological pathways involved,” Brooks says.

"Real-Life Nutrigenomics"

In the equine industry, nutrigenomics is in its infancy. In other health fields, however, nutrigenomics is progressing rapidly. In small animals, for example, it is being used to manage obesity. According to one study published in the June 2013 Journal of Animal Science, diets including probiotics, green tea extract, or increased protein levels apparently modify the expression of genes related to glucose and lipid metabolism in fat tissues. Those study results also suggest that changing gene expression through dietary intervention could become a useful tool for managing and preventing obesity.

Stacey Oke, DVM, MSc

“Gene chips and gene sequencing technologies allow us to rapidly (within a few weeks) measure changes in gene expression, either increases or decreases, of thousands of different genes in a single experiment,” she continues. “This is a major advance considering we used to have to measure those changes in each individual gene, and each of those individual experiments used to take hours to perform.”

This method can help scientists rapidly uncover new interactions between diet and gene expression without needing to know the exact gene to look for.

DNA chips can also allow mapping of genes causing heritable dietary issues: “We (are using the chip) … to examine approximately 50,000 genetic markers that might contribute to equine metabolic syndrome (EMS) and equine Cushing’s disease (pituitary pars intermedia disorder, PPID),” Brooks says. “The goal of these studies is to identify horses at risk of developing EMS or PPID before they begin to show signs of the diseases in order to prevent their development of tragic secondary complications like laminitis.”

Although research is currently lacking in the equine field, scientists believe many other equine diseases/conditions in addition to those listed can benefit from nutrigenomics, including obesity and cancer.

The Future of Nutrigenomics

Brooks says an ultimate goal in the field of equine nutrigenomics is to tailor individual horses’ diets based on their genetic information so that they grow and develop appropriately, helping them avoid some of the developmental and metabolic issues described.

But that doesn’t mean scientists aren’t also using this technology to find ways to maximize the wellness of healthy adult horses.

“How individual horses use their diet can be influenced by their environment as well as internal factors, such as the normal bacteria in their gastrointestinal tracts,” Brooks says. “Together, the external and internal factors are difficult to study; however, if we are able to ‘tease out’ the genetic components involved in how nutrients are utilized by the horse, then an equation for a healthy horse can be developed to allow us to more accurately study all of the important environmental factors.”

As wonderful as this technology is, Brooks and Brennan do highlight several hurdles nutrigenomics researchers face.

“One limitation associated with research in this field is that we are not always able to obtain sufficient samples from target tissues,” Brennan says. “Because it is hard to ethically justify euthanizing healthy horses, sampling is limited to easily obtained tissues like white blood cells or skeletal muscle. The question then becomes, is the sample truly relative to what nutrient you are looking at?” In other words, can we look at how a nutrient is going to impact bone density by looking at a blood cell?

Brooks concurs and adds, “We have the technology and the time. What is currently limiting us is a large enough number of study subjects—horses with good data sets on their dietary needs.” (To learn about current equine studies at Cornell and how you and your horse can become involved, visit http://blogs.cornell.edu/equinegenetics/research.)

Another current major limitation, according to Brennan, is the “annotation” of the equine genome.

“The equine genome has been sequenced, but we don’t have a lot of information yet as to what each gene is,” she explains. “For instance, we might see that Gene A is upregulated fourfold, but we may not know what Gene A is. Annotation of the gene chip is really our bottleneck right now.”

Take-Home Message

In the near future, researchers might be able to rapidly analyze a horse’s genetic material to determine which genes diet alterations influence. Then veterinarians, nutritionists, and owners can potentially devise better feeding strategies and improve nutritional supplements. Ultimately, researchers anticipate nutrigenomics will enable owners and trainers to tailor their horses’ diets easily based on each animal’s own DNA.

“We still haven’t fully capitalized on the information currently available to us, and the equine genome is the doorway to our future pursuits,” Brooks says. “Right now we are limited by the number of samples from horses with various conditions and available funding for equine research, rather than by the equipment and technology. The key to our success is the partnership between nutritionists, veterinarians, and owners together with geneticists to extract as much information as possible from the equine genome and the equine chips.”

About the Author

Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.

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